Some glycosaminoglycans (GAGs), such as heparin and heparin-like compounds inhibit the proliferation of several cell types, including smooth muscle cells, cervical epithelial cells and fibroblasts (1-3). In order to establish which domain of the hepar-in molecule is specifically responsible for the anti-proliferative activity, several strategies have been adopted such as: chemical modification or fractionation of the heparin molecule into low molecular weight fragments or synthesis of oligosaccharides with a defined chemical structure (4-6). In the present study we attempted to determine the role of N- and 0- linked sulfate groups on the anti-proliferative and anticoagulant effect of heparin. To that purpose we modified the molecule to produce N-desulfated, 0-desulfated compounds. The anti-proliferative activity of these modified heparins was compared to that of low molecular weight heparins obtained by depolymerization, heparan sulfate as N-acetylated compound with glucuronic acid and heparin. Since the anti-proliferative effect of heparin depends also on the cell type, we used two different cell types: BHK-21 (hamster fibroblasts) and human arterial SMC (smooth muscle cells), that were found to exhibit a high or intermediate sensitivity to heparin (3,7).
Effect of the desulfation of heparin on its anticoagulant and anti-proliferative activity / Tiozzo, Roberta; Cingi, Mr; Reggiani, D; Andreoli, T; CALANDRA BUONAURA, Sebastiano; Milani, Mr; Piani, S; Marchi, E; Barbanti, M.. - In: THROMBOSIS RESEARCH. - ISSN 0049-3848. - STAMPA. - 70:(1993), pp. 99-106.
Effect of the desulfation of heparin on its anticoagulant and anti-proliferative activity
TIOZZO, Roberta;CALANDRA BUONAURA, Sebastiano;
1993
Abstract
Some glycosaminoglycans (GAGs), such as heparin and heparin-like compounds inhibit the proliferation of several cell types, including smooth muscle cells, cervical epithelial cells and fibroblasts (1-3). In order to establish which domain of the hepar-in molecule is specifically responsible for the anti-proliferative activity, several strategies have been adopted such as: chemical modification or fractionation of the heparin molecule into low molecular weight fragments or synthesis of oligosaccharides with a defined chemical structure (4-6). In the present study we attempted to determine the role of N- and 0- linked sulfate groups on the anti-proliferative and anticoagulant effect of heparin. To that purpose we modified the molecule to produce N-desulfated, 0-desulfated compounds. The anti-proliferative activity of these modified heparins was compared to that of low molecular weight heparins obtained by depolymerization, heparan sulfate as N-acetylated compound with glucuronic acid and heparin. Since the anti-proliferative effect of heparin depends also on the cell type, we used two different cell types: BHK-21 (hamster fibroblasts) and human arterial SMC (smooth muscle cells), that were found to exhibit a high or intermediate sensitivity to heparin (3,7).Pubblicazioni consigliate
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